During the past decade there has been a significant change in our view of synaptic function: it has now become apparent that the synaptically associated astrocyte, is key for the control of synaptic transmission. Consequently, a concept of tripartite synaptic transmission has been proposed. Though the concept has been formulated, we are at the very early days in our understanding of the relative roles of presynaptic, postsynaptic and astrocytic elements in the control of functional synaptic transmission. The goal of this Conte center is to bring together a team of talented and experienced investigators to focus collaborative studies on the tripartite synapse. Our goal is to change the landscape of thinking by testing the overriding hypothesis that "Bidirectional signaling between astrocytes and pre- and postsynaptic neurons regulates the function of the tripartite synapse". To address this hypothesis we propose four collaborative projects: Project #1 (Coulter, project director), will study the role of astrocytes in regulating the loading of vesicles with transmitter by controlling the recycling of neurotransmitter substrates. Project #2 (Eberwine, project director) will take a longer-term view of the astrocyte by studying the gene expression profiles of astrocytes, and investigate transmitter-dependent regulation of translation within astrocytes and their processes. Project #3 (Haydon, project director) will study the role of synaptotagmin IV in releasing gliotransmitters from astrocytes and how the short and long-term regulation of this protein controls synaptic transmission and plasticity. Because imaging and photolysis will be critical for many of the studies performed in this Conte Center we will include a photochemistry core (Ellis-Davies) within the center that will provide and develop new caged compounds for photo-release by two-photon photolysis. Collectively these projects will dramatically enhance our understanding of the tripartite synapse leading to new insights into the control of the functional circuitry of the brain.